Amino acid N-carboxyanhydrides, also called Leuchs' anhydrides, are a family of
heterocyclicorganic compounds derived from
amino acids. They are white, moisture-reactive solids. They have been evaluated for applications the field of
biomaterials.[1][2][3]
They were first synthesized by
Hermann Leuchs by heating an N-ethoxycarbonyl or N-methoxycarbonyl
amino acid chloride in a vacuum at 50-70 °C:[5][6]
A moisture-tolerant route to unprotected NCAs employs
epoxides as scavengers of hydrogen chloride.[7]
This synthesis of NCAs is sometimes called the Leuchs method. The relatively high temperatures necessary for this cyclization results in the decomposition of several NCAs. Of several improvements, one notable procedure involves treating an unprotected amino acid with
phosgene or its trimer.[8][9][10]
Reactions
NCAs are prone to hydrolysis to the parent amino acid:
RCHNHC(O)OC(O) + H2O → H2NCH(R)CO2H + CO2
Some derivatives however tolerate water briefly.[7]
NCAs convert to homopolypeptides ( [N(H)CH(R)CO)]n) through ring-opening polymerization:[1][2][3][11][12][13][14]
iang J, Zhang X, Fan Z, Du J (2019-10-15). "Ring-Opening Polymerization of N-Carboxyanhydride-Induced Self-Assembly for Fabricating Biodegradable Polymer Vesicles". ACS Macro Letters. 8 (10): 1216–1221.
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abcdKricheldorf HR (September 2006). "Polypeptides and 100 years of chemistry of alpha-amino acid N-carboxyanhydrides". Angewandte Chemie. 45 (35): 5752–84.
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^Lyndon C. Xavier, Julie J. Mohan, David J. Mathre, Andrew S. Thompson, James D. Carroll, Edward G. Corley, and Richard Desmond (1997). "(S)-Tetrahydro-1-methyl-3,3-diphenyl-1h,3h-pyrrolo-[1,2-c] [1,3,2]oxazaborole-borane Complex". Organic Syntheses. 74: 50.
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^Gibson MI, Hunt GJ, Cameron NR (September 2007). "Improved synthesis of O-linked, and first synthesis of S- linked, carbohydrate functionalised N-carboxyanhydrides (glycoNCAs)". Organic & Biomolecular Chemistry. 5 (17): 2756–7.
doi:
10.1039/b707563d.
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abDimitrov I, Schlaad H (December 2003). "Synthesis of nearly monodisperse polystyrene-polypeptide block copolymers via polymerisation of N-carboxyanhydrides". Chemical Communications (23): 2944–2945.
doi:
10.1039/b308990h.
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^Song Z, Han Z, Lv S, Chen C, Chen L, Yin L, Cheng J (October 2017). "Synthetic Polypeptides: from Polymer Design to Supramolecular Assembly and Biomedical Application". Chemical Society Reviews. 46 (21): 6570–6599.
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^Kopecek J (September 2003). "Smart and genetically engineered biomaterials and drug delivery systems". European Journal of Pharmaceutical Sciences. 20 (1): 1–16.
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^Lu H, Wang J, Song Z, Yin L, Zhang Y, Tang H, et al. (January 2014). "Recent Advances in Amino Acid N-Carboxyanhydrides and Synthetic Polypeptides: Chemistry, Self-Assembly and Biological Applications". Chemical Communications. 50 (2): 139–55.
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^Katakai R (September 1975). "Peptide synthesis using o-nitrophenylsulfenyl N-carboxy alpha-amino acid anhydrides". The Journal of Organic Chemistry. 40 (19): 2697–2702.
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^Deming TJ (1998). "Amino Acid Derived Nickelacycles: Intermediates in Nickel-Mediated Polypeptide Synthesis". Journal of the American Chemical Society. 120 (17): 4240–4241.
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^Taillades J, Beuzelin I, Garrel L, Tabacik V, Bied C, Commeyras A (February 1998). "N-carbamoyl-alpha-amino acids rather than free alpha-amino acids formation in the primitive hydrosphere: a novel proposal for the emergence of prebiotic peptides". Origins of Life and Evolution of the Biosphere. 28 (1): 61–77.
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